Vitamin B12 is a water soluble vitamin that plays a role in mammalian growth, hematopoiesis, production of epithelial cells, and maintenance of the nervous system. It was first isolated from liver concentrate in 1948 and structurally elucidated in the late 1950's.
Cyanocobalamin is a form of vitamin B12 and is one of the class of B12 vitamins or cobalamin compounds that includes vitamin B12a (hydroxocobalamin), vitamin B12b (aquacobalamin), vitamin B12c (nitrilocobalamin), methyl B12 (methylcobalamin) and coenzyme B12 (5′deoxyadenosine cobalamin). Cyanocobalamin and hydroxocobalamin are the principal members of the class and the most widely employed in compositions used to treat vitamin B12 deficiency and disorders that are related to this deficiency. Such disorders include anemias (most commonly pernicious anemia) and diphyllobothrium latum (fish tapeworm) infestation of the intestine, a disorder with symptomology that mimics pernicious anemia.
Several routes of administration of vitamin B12 are known. Among these are parenterally, including intramuscular and subcutaneous injection, orally as a component of a tablet or solution, and nasally, as a component of a nasal spray or gel. Although the minimum daily dietary requirement of vitamin B12 is approximately 0.1 μg for a healthy human, therapeutic administration of vitamin B12 is typically in significantly larger doses. For example, the prescribed initial therapeutic dose is generally from about 100 μg to about 1000 μg, and is most often administered by intramuscular injection. Subsequent vitamin B12 maintenance therapy may be by injection or by oral administration of a cobalamin composition. Use of vitamin B12 injections for maintenance therapy has obvious disadvantages, including the inconvenience and pain associated with the injection that typically must be administered by medical personnel. Orally administered cobalamin compositions may fail to be adequately absorbed in the patient, particularly in those in which secretion or utilization of intrinsic factor is inadequate.
Intranasal administration of cobalamin compositions for vitamin B12 maintenance therapy offers advantages over these alternative routes of administration. Typically, such therapy includes relatively infrequent, high dose nasal administration of a cobalamin composition. For example, NASCOBAL nasal spray solution containing 0.5% by weight cyanocobalamin is administered in one nostril once weekly in a dose of 500 μg (i.e., 500 μg cyanocobalamin per 0.1 mL actuation of the spray bottle pump).
Although maintenance therapy with vitamin B12 nasal compositions has proven generally effective, those undergoing such therapy may experience some irritation of the nasal mucosa and discomfort due, in part, to the high dosage of the cobalamin compound typically administered as well as preservatives and other additives often present in these compositions. Moreover, effective vitamin B12 maintenance therapy would be enhanced if more stable or even blood serum levels of vitamin B12 could be attained through intranasal administration of a cobalamin composition. Accordingly, a need persists for improvements in vitamin B12 nasal compositions and methods of nasal administration of such compositions in the treatment of vitamin B12 deficiency and various vitamin B12 deficiency-mediated disorders.